IL-23 in health and disease

© Springer Japan 2014. The discovery of IL-23 and characterization of the biology governed by this cytokine has led to dramatic new insights within immunology. IL-23 is central to the pathogenesis of many immune-mediated inflammatory disorders and was shown to act via a novel IL-17-producing T helper subset, the Th17 cell. Many innate cells also respond to IL-23 and are important in both resistance to infection and in mediating autoimmune pathology. These cells are characterized by expression of RORγt transcription regulator and include subsets of γδ T cells, natural killer (NK) cells, innate lymphoid cells in the intestine and a recently described entheseal resident cell that resides at a key site for rheumatic illness. Stimulation of these various cells by IL-23 induces severe inflammation, much of which is mediated by the signature cytokines, including IL-17 and IL-22. Exploration of the biology of IL-23 has thus led to the identification of novel immune cell subsets as well as new paradigms for disease localization based upon the distribution of IL-23- responder populations. These new concepts are at the core of novel therapeutic strategies based upon neutralization of IL-23 or IL-17, which are showing encouraging results for treatment of psoriasis, multiple sclerosis, rheumatoid arthritis, and ankylosing spondylitis.